Technical Note: Measurement of the tropical UTLS composition in presence of clouds using millimetre-wave heterodyne spectroscopy

The MARSCHALS (Millimetre-wave Airborne Receiver for Spectroscopic CHaracterisation of Atmospheric Limb-Sounding) project has the general objectives of demonstrating the measurement capabilities of a limb viewing instrument working in the millimetre and sub-millimetre spectral regions (from 294 to 349 GHz) for the study of the Upper Troposphere – Lower Stratosphere (UTLS). MARSCHALS has flown on board the M-55 stratospheric aircraft (Geophysica) in two measurements campaigns. Here we report the results of the analysis of MARSCHALS measurements during the SCOUT-O3 campaign held in Darwin (Australia) in December 2005 obtained with MARC (Millimetrewave Atmospheric-Retrieval Code). MARSCHALS measured vertical distributions of temperature, water vapour, ozone and nitric acid in the altitude range from 10 to 20 km in presence of clouds that obscure measurements in the middle infrared spectroscopic region. The minimum altitude at which the retrieval has been possible is determined by the high water concentration typical of the tropical region rather than the extensive cloud coverage experienced during the flight. Water has been measured from 10 km to flight altitude (~18 km) with a 10% accuracy, ozone from 14 km to flight altitude with accuracy ranging from 10% to 60%, while the retrieval of nitric acid has been possible with an accuracy not better than 40% only from 16 km to flight altitude due to the low signal to noise ratio of its emission in the analysed spectral region. The results have been validated using measurement made in a less cloudy region by MIPAS-STR, an infrared limb-viewing instrument on board the M-55, during the same flight

Distribution of Fos in rat brain resulting from endogenously-generated angiotensin II

Distribution of Fos in rat brain resulting from endogenously-generated angiotensin II. The beta adrenergic agonist isoproterenol has been used in these studies to elevate circulating levels of angiotensin II. Neurons in the brain responsive to the subcutaneous infusion of isoproterenol were identified using an antibody to Fos, the protein product of c-fos which is now used extensively as a marker of activated neurons. Fos-positive neurons were present in a range of specific forebrain and hind brain regions. Infusion of losartan (an angiotensin II type receptor antagonist) showed that neurons in the lamina terminalis were activated directly or indirectly by angiotensin II, whereas other neurons in the hypothalamus and brain stem were responsive as a consequence of the peripheral vasodilation caused by isoproterenol. The distribution of activated neurons in the lamina terminalis was consistent with that of neurons thought to be involved in water drinking

Combination cannabinoid and opioid receptor antagonists improves metabolic outcomes in obese mice.

The CB1 receptor antagonist, rimonabant, causes weight loss but also produces undesirable psychiatric side effects. We investigated using a combination of rimonabant with the opioid receptor antagonists naloxone and norBNI to treat the metabolic sequelae of long-term high fat diet feeding in mice. This combination has previously been shown to have positive effects on both weight loss and mood related behaviour. Diet-induced obese mice were treated chronically with either low dose rimonabant (1mg/kg) or the combination of rimonabant, naloxone and norBNI (rim nal BNI). After 6 days of treatment, glucose and insulin tolerance tests were performed and body composition analysed using DEXA. Changes in BAT thermogenesis were assessed using implantable radio telemetry probes. Behavioural responses to acute rimonabant or rim nal BNI were examined in the forced swim test and elevated plus maze. Separately, we assessed shifts in Fos immunoreactivity in response to rimonabant or rim nal BNI. Rim nal BNI was significantly better than rimonabant treatment alone at reducing body weight and food intake. In addition, it improved fasting blood glucose and fat mass. Acute low dose rimonabant did not alter behaviour in either the forced swim test or elevated plus maze. Combination rim nal BNI reversed the behavioural effects of high dose (10mg/kg) rimonabant in obese mice. Rim nal BNI altered Rimonabant-induced Fos in a number of nuclei, with particular shifts in expression in the central and basolateral amygdala, and insular cortex. This study demonstrates that the combination of rimonabant, naloxone and norBNI is effective at producing weight loss over a sustained period of time without altering performance in standardised mouse behaviour tests. Fos expression patterns offer insight into the neuroanatomical substrates subserving these physiological and behavioural changes. These results indicate that CB1-targeted drugs for weight loss may still be feasible

Adolescent inhalant abuse results in adrenal dysfunction and a hypermetabolic phenotype with persistent growth impairments

Abstract not availableRose Crossin, Zane B. Andrews, Natalie A. Sims, Terence Pang, Michael Mathai, Jonathan H. Gooi, Aneta Stefanidis, Brian J. Oldfield, Andrew J. Lawrence, Jhodie R. Dunca

Mechanisms underlying the efficacy of a rodent model of vertical sleeve gastrectomy — A focus on energy expenditure

Objective: Bariatric surgery remains the only effective and durable treatment option for morbid obesity. Vertical Sleeve Gastrectomy (VSG) is currently the most widely performed of these surgeries primarily because of its proven efficacy in generating rapid onset weight loss, improved glucose regulation and reduced mortality compared with other invasive procedures. VSG is associated with reduced appetite, however, the relative importance of energy expenditure to VSG-induced weight loss and changes in glucose regulation, particularly that in brown adipose tissue (BAT), remains unclear. The aim of this study was to investigate the role of BAT thermogenesis in the efficacy of VSG in a rodent model. Methods: Diet-induced obese male Sprague–Dawley rats were either sham-operated, underwent VSG surgery or were pair-fed to the food consumed by the VSG group. Rats were also implanted with biotelemetry devices between the interscapular lobes of BAT to assess local changes in BAT temperature as a surrogate measure of thermogenic activity. Metabolic parameters including food intake, body weight and changes in body composition were assessed. To further elucidate the contribution of energy expenditure via BAT thermogenesis to VSG-induced weight loss, a separate cohort of chow-fed rats underwent complete excision of the interscapular BAT (iBAT lipectomy) or chemical denervation using 6-hydroxydopamine (6-OHDA). To localize glucose uptake in specific tissues, an oral glucose tolerance test was combined with an intraperitoneal injection of 14C-2-deoxy-d-glucose (14C-2DG). Transneuronal viral tracing was used to identify 1) sensory neurons directed to the stomach or small intestine (H129-RFP) or 2) chains of polysynaptically linked neurons directed to BAT (PRV-GFP) in the same animals. Results: Following VSG, there was a rapid reduction in body weight that was associated with reduced food intake, elevated BAT temperature and improved glucose regulation. Rats that underwent VSG had elevated glucose uptake into BAT compared to sham operated animals as well as elevated gene markers related to increased BAT activity (Ucp1, Dio2, Cpt1b, Cox8b, Ppargc) and markers of increased browning of white fat (Ucp1, Dio2, Cited1, Tbx1, Tnfrs9). Both iBAT lipectomy and 6-OHDA treatment significantly attenuated the impact of VSG on changes in body weight and adiposity in chow-fed animals. In addition, surgical excision of iBAT following VSG significantly reversed VSG-mediated improvements in glucose tolerance, an effect that was independent of circulating insulin levels. Viral tracing studies highlighted a patent neural link between the gut and BAT that included groups of premotor BAT-directed neurons in the dorsal raphe and raphe pallidus. Conclusions: Collectively, these data support a role for BAT in mediating the metabolic sequelae following VSG surgery, particularly the improvement in glucose regulation, and highlight the need to better understand the contribution from this tissue in human patients

Erratum: Gonadotropin-Inhibitory Hormone Is a Hypothalamic Peptide That Provides a Molecular Switch between Reproduction and Feeding

<b><i>Objective:</i></b> Gonadotropin-inhibitory hormone (GnIH)-3 is a neuropeptide that plays a major role in the regulation of reproduction and feeding in mammals. <b><i>Materials and Methods:</i></b> We measured endocrine and behavioural parameters of reproduction in sheep, and sexual behaviour in sheep, mice and cynomolgus monkeys. In addition, GnIH gene expression (in situ hybridization) was examined in ewes, and effects of GnIH-3 on food intake and energy expenditure were measured in various species. GnIH-3 was infused (i.v.) into ewes after an i.m. injection of estradiol benzoate to determine whether the peptide blocks the surge in luteinizing hormone (LH) secretion. <b><i>Results:</i></b> GnIH gene expression was reduced in the preovulatory period in ewes. Infusion (i.v.) of GnIH-3 blocked the estrogen-induced LH surge (in ewes). Intracerebroventricular infusion had no effect on female or male sexual behaviour in each of the three species, but increased food intake. There were no effects on energy expenditure in sheep or rats. GnIH increased fos protein (immunohistochemistry) was seen in orexigenic neurons (in sheep and rats), but also in anorexigenic neurons (in sheep). <b><i>Conclusions:</i></b> GnIH-3 reduces reproductive hormone levels and increases food intake in mammals without reducing energy expenditure. There is minimal effect on reproductive behaviour. The dual effect on reproduction and feeding suggests that GnIH-3 provides a molecular switch between these two functions. Blockade of the positive feedback effect of estrogen with parenteral infusion indicates that this peptide may have utility as a blocker of reproductive function in mammals